Project Summary Despite the high rates of depression, anxiety, and dysregulated emotion characterized by agitation, irritation, and mood swings in Alzheimer's Disease (AD), few studies have asked how emotional responses may change with the development of AD. Recent work has shown prolonged emotional responses in AD patients' self-report that persist even after memory for the emotional provocation has decayed, and an impaired ability to regulate facial responses to a loud startling noise when instructed to do so. Whether differences in the reactivity to and regulation of emotion are observed over the course of the development of the disease as memory and cognition start to fail remains unknown. Similarly, whether potential differences in the time course of emotion relate to changes in emotional memory biases or to tau and amyloid deposition in brain regions important for emotion are important but unmapped domains of emotion processing. This proposal will use objective measures of emotional responding - facial electromyography (facEMG) and functional magnetic resonance imaging (fMRI) - to measure the temporal dynamics of negative and positive emotional responses in 100 individuals with preclinical AD. Preclinical AD will have been previously confirmed with tau and amyloid positron emission tomography (PET) obtained in a Wisconsin Registry for Alzheimer's Prevention (WRAP) substudy under a separately funded protocol. In this proposal, processes occurring directly in response to emotional stimuli (emotional reactivity) will be differentiated from processes occurring after offset of the stimuli (emotional recovery) in both facEMG and fMRI measures. These data will be combined with the extant longitudinal cognitive and imaging data from the WRAP study and compared to normative data previously collected in our laboratory from the Midlife in the US (MIDUS) study using the identical procedures and methods as this protocol. FacEMG and fMRI measures of emotional reactivity to and recovery from negative and positive stimuli will be examined in relation to (i) tau and amyloid deposition in emotion regulation brain circuitry (e.g. the amygdala, hippocampus, anterior cingulate cortex, and other regions of prefrontal cortex), (ii) longitudinal cognitive and executive function changes, (iii) later memory for the emotional stimuli, and (iv) compared with normative emotional reactivity and recovery data from the MIDUS study. In all analyses we will explore age and gender interactions. We predict that individuals with preclinical AD will exhibit impaired emotion regulation, which will be proportional to the pathological protein burden and cognitive and memory changes. Because impaired emotion regulation may exacerbate and prolong stress responses which have been linked to neurodegeneration such as occurs in AD, gaining a better understanding of emotional processes in preclinical AD is critical for development of target interventions that may prove useful for slowing and/or preventing the progression to full clinical onset as well as guide treatment and care decisions.